136553-96-3

Basic information

• Product Name: JKC-301
• Synonyms: JKC-301;CYCLO(-D-ASP-PRO-D-ILE-LEU-D-TRP);JKC 301 (CYCLO-[D-ASP-PRO-D-LLE-LEU-D-TR P]), SYNTHETIC, >99% PURITY
• CAS NO: 136553-96-3
• Molecular Formula: C32H44N6O7
• Molecular Weight: 624.73
• Mol File: 136553-96-3.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 1052.2±65.0 °C(Predicted)
• Appearance: /
• Density: 1.31±0.1 g/cm3(Predicted)
• Storage Temp.: -15°C
• PKA: 4.04±0.10(Predicted)
• CAS DataBase Reference: JKC-301(CAS DataBase Reference)
• NIST Chemistry Reference: JKC-301(136553-96-3)
• EPA Substance Registry System: JKC-301(136553-96-3)

Safety Data

• Hazardous Substances Data: 136553-96-3(Hazardous Substances Data)

Upstream product

• 1026240-78-7 (R)-3-[(R)-2-Amino-3-(1H-indol-3-yl)-propionylamino]-4-{(S)-2-[(1R,2S)-1-((S)-1-azidocarbonyl-3-methyl-butylcarbamoyl)-2-methyl-butylcarbamoyl]-pyrrolidin-1-yl}-4-oxo-butyric acid tert-butyl ester 
• 1026352-38-4 (R)-3-[(R)-2-Amino-3-(1H-indol-3-yl)-propionylamino]-4-{(S)-2-[(1R,2R)-1-((S)-1-azidocarbonyl-3-methyl-butylcarbamoyl)-2-methyl-butylcarbamoyl]-pyrrolidin-1-yl}-4-oxo-butyric acid tert-butyl ester 
• 1027248-70-9 (R)-3-[(R)-2-Amino-3-(1H-indol-3-yl)-propionylamino]-4-{(S)-2-[(1R,2R)-1-((S)-1-hydrazinocarbonyl-3-methyl-butylcarbamoyl)-2-methyl-butylcarbamoyl]-pyrrolidin-1-yl}-4-oxo-butyric acid tert-butyl ester 

Relevant articles and documents

Structure-activity relationships of cyclic pentapeptide endothelin A receptor antagonists

Analogues of the natural product endothelin A (ET(A)) receptor antagonists cyclo(-D-Trp1-D-Glu2-Ala3-D-Va14-Leu5-) (1) and cyclo(-D-Trp1-D-Glu2- Ala3-D-alloIle4-Leu5-) (2) were prepared and tested for inhibitory activity against [125I]endothelin (ET-1) binding to protein ET(A) receptors. The DDLDL chirality sequence of the natural products appeared to be critical for inhibitory activity because conversion of either D-Trp or D- Glu (or both) in 1 to the corresponding L-isomer(s) abolished this property. Systematic modifications at each position of the natural products clarified the structure-activity relationships and led to highly potent and selective ET(A) receptor antagonists. Most replacements of D-Trp1 and Leu5 with other amino acids caused a significant loss of inhibitory activity. In contrast, replacement of D-Glu2 with D-Asp2 enhanced the activity. With regard to the Ala3 position, all analogues with imino acids, independent of being cyclic or acyclic, showed higher affinities than did the amino acid analogues. In addition, most replacements with amino acids, which had various functional groups in their side chains, did not significantly modify ET(A) binding affinity. The D-Va14/D-alloIle4 position was very important for inhibitory activity, and a β-position branched D-amino acid or a D-heteroarylglycine was preferable at this position. Among synthesized cyclic pentapeptides, compound 36 (BQ-518) was the most potent ETA receptor antagonist, with a pA2 of 8.1 against ET-1-induced vasoconstriction in isolated porcine coronary arteries. This compound also showed the greatest selectivity between ET(A) and ET(B) receptors (IC50 for human ET(A) = 1.2 nM, IC50 for human ET(B) = 55 μM). In contrast, compound 8 (BQ-123) is a highly soluble, potent, and selective ET(A) receptor antagonist (pA2 = 7.4, IC50 for human ET(A) = 8.3 nM, IC50 for human ET(B) = 61 μM). The sodium salt of 8 is practically freely soluble in saline. These compounds are useful tools for not only in vitro but also in vivo pharmacological studies.